The antifibrotic potential of pirfenidone (5-methyl-1-phenyl-2-[1H]-pyridone) was examined in a single intratracheal bleomycin dose hamster model of pulmonary fibrosis. Bleomycin-induced fibrosis and the effectiveness of pirfenidone treatment were assessed by measuring pulmonary functions (Cqst, TLC, VC, IC, FRC, RV) and the level of hydroxyproline in whole lung homogenates. Thirty-five male golden Syrian hamsters were randomized into four experimental groups: saline instilled and fed a control diet of rat chow (SCD, n = 8); saline instilled and fed the control diet containing 0.5% (w/w) pirfenidone (SPD, n = 8); bleomycin instilled and fed the control diet (BCD, n = 7); and bleomycin instilled and fed the control diet containing 0.5% pirfenidone (BPD, n = 10). Twenty-one days following bleomycin instillation Cqst/TLC, TLC, VC, and IC were significantly reduced and total lung hydroxyproline levels were significantly increased in the BCD and BPD groups as compared with the SCD and SPD groups, respectively. Pirfenidone ingestion significantly attenuated these bleomycin-induced pertubations in pulmonary functions and lung hydroxyproline levels (BCD versus BPD). The data obtained in this study provide evidence of the benefical effects of pirfenidone in the hamster model of bleomycin-induced pulmonary fibrosis both at the functional and biochemical level.